Ashkan Shoamanesh, Thalia S Field, Shelagh B Coutts, Mukul Sharma, David Gladstone, Robert G Hart, Giuseppe Boriani, David J Wright, Christian Sticherling, David H Birnie, Michael R Gold, Julia W Erath, Valentina Kutyifa, Rajibul Mian, Alexander P Benz, Christopher B Granger, William F McIntyre, Stuart J Connolly, Jens Cosedis Nielsen, Marco Alings, Jeff S Healey
{"title":"Apixaban versus aspirin for stroke prevention in people with subclinical atrial fibrillation and a history of stroke or transient ischaemic attack: subgroup analysis of the ARTESiA randomised controlled trial","authors":"Ashkan Shoamanesh, Thalia S Field, Shelagh B Coutts, Mukul Sharma, David Gladstone, Robert G Hart, Giuseppe Boriani, David J Wright, Christian Sticherling, David H Birnie, Michael R Gold, Julia W Erath, Valentina Kutyifa, Rajibul Mian, Alexander P Benz, Christopher B Granger, William F McIntyre, Stuart J Connolly, Jens Cosedis Nielsen, Marco Alings, Jeff S Healey","doi":"10.1016/s1474-4422(24)00475-7","DOIUrl":"https://doi.org/10.1016/s1474-4422(24)00475-7","url":null,"abstract":"<h3>Background</h3>People with subclinical atrial fibrillation are at increased risk of stroke, albeit to a lesser extent than those with clinical atrial fibrillation, leading to an ongoing debate regarding the benefit of anticoagulation in these individuals. In the ARTESiA trial, the direct-acting oral anticoagulant apixaban reduced stroke or systemic embolism compared with aspirin in people with subclinical atrial fibrillation, but the risk of major bleeding was increased with apixaban. In a prespecified subgroup analysis of ARTESiA, we tested the hypothesis that people with subclinical atrial fibrillation and a history of stroke or transient ischaemic attack, who are known to have an increased risk of recurrent stroke, would show a greater benefit from oral anticoagulation for secondary stroke prevention compared with those without a history of stroke or transient ischaemic attack.<h3>Methods</h3>ARTESiA is a double-blind, double-dummy, randomised controlled trial conducted at 247 sites in 16 countries across Europe and North America. Adults aged 55 years or older with device-detected subclinical atrial fibrillation lasting from 6 min to 24 h and a CHA<sub>2</sub>DS<sub>2</sub>-VASc score of 3 or higher were randomly assigned using an interactive web-based system to oral apixaban 5 mg twice per day or oral aspirin 81 mg once per day. The primary efficacy outcome was stroke or systemic embolism, and the primary safety outcome was major bleeding, assessed as absolute risk differences. Analyses were by intention to treat. ARTESiA is registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> (<span><span>NCT01938248</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>) and is completed; this report presents a prespecified subgroup analysis in people with a history of stroke or transient ischaemic attack.<h3>Findings</h3>Between May 7, 2015, and July 30, 2021, 4012 people with subclinical atrial fibrillation were randomly allocated either apixaban (n=2015) or aspirin (n=1997). A history of stroke or transient ischaemic attack was present in 346 (8·6%) participants (172 assigned to apixaban and 174 to aspirin), among whom the annual rate of stroke or systemic embolism was 1·20% (n=7; 95% CI 0·48 to 2·48) with apixaban versus 3·14% (n=18; 1·86 to 4·96) with aspirin; (hazard ratio [HR] 0·40, 95% CI 0·17 to 0·95). In participants without a history of stroke or transient ischaemic attack (n=3666; 1843 assigned to apixaban and 1823 to aspirin), the annual rate of stroke or systemic embolism was 0·74% (n=48; 95% CI 0·55 to 0·98) with apixaban versus 1·07% (n=68; 95% CI 0·83 to 1·36) with aspirin (HR 0·6","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ali A Habib, Chongbo Zhao, Inmaculada Aban, Marcondes Cavalcante França, Jorge Gustavo José, Gerd Meyer zu Hörste, Elżbieta Klimiec-Moskal, Michael T Pulley, Darío Tavolini, Petranka Krumova, Siân Lennon-Chrimes, Jillian Smith, Gian-Andrea Thanei, Kathleen Blondeau, Ivana Vodopivec, Gil I Wolfe, Hiroyuki Murai
{"title":"Safety and efficacy of satralizumab in patients with generalised myasthenia gravis (LUMINESCE): a randomised, double-blind, multicentre, placebo-controlled phase 3 trial","authors":"Ali A Habib, Chongbo Zhao, Inmaculada Aban, Marcondes Cavalcante França, Jorge Gustavo José, Gerd Meyer zu Hörste, Elżbieta Klimiec-Moskal, Michael T Pulley, Darío Tavolini, Petranka Krumova, Siân Lennon-Chrimes, Jillian Smith, Gian-Andrea Thanei, Kathleen Blondeau, Ivana Vodopivec, Gil I Wolfe, Hiroyuki Murai","doi":"10.1016/s1474-4422(24)00514-3","DOIUrl":"https://doi.org/10.1016/s1474-4422(24)00514-3","url":null,"abstract":"<h3>Background</h3>Evidence from preclinical studies suggests that IL-6 signalling has the potential to modulate immunopathogenic mechanisms upstream of autoantibody effector mechanisms in patients with generalised myasthenia gravis. We aimed to assess the safety and efficacy of satralizumab, a humanised monoclonal antibody targeting the IL-6 receptor, in patients with generalised myasthenia gravis.<h3>Methods</h3>LUMINESCE was a randomised, double-blind, placebo-controlled, multicentre, phase 3 study at 105 sites, including hospitals and clinics, globally. Eligible patients were aged 12 years and older, with seropositive generalised myasthenia gravis (autoantibodies to the acetylcholine receptor [AChR-IgG], muscle-specific kinase [MuSK-IgG], or low-density lipoprotein receptor-related protein 4 [LRP4-IgG]), a Myasthenia Gravis Foundation of America severity class II–IV, a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of 5 or more (non-ocular contribution >50%), and use of stable background therapy. Patients were randomly assigned (1:1) with a permuted-block randomisation method to receive subcutaneous satralizumab (120 mg for bodyweight ≤100 kg; 180 mg for bodyweight >100 kg) or placebo at weeks 0, 2, 4, and every 4 weeks thereafter until week 24. Randomisation was stratified according to background therapy, autoantibody type, and geographical region. The primary efficacy endpoint was mean change from baseline in total MG-ADL score at week 24 in the modified intention-to-treat population (all randomised AChR-IgG-positive patients who completed at least one post-baseline MG-ADL assessment). Safety was assessed in all randomly assigned patients who received at least one dose of study drug. The open-label extension was terminated early because of the sponsor's decision to halt further development of satralizumab for treatment of generalised myasthenia gravis. This trial is registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, <span><span>NCT04963270</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>, and EudraCT, 2020-004436-21.<h3>Findings</h3>Between Oct 19, 2021, and Aug 15, 2023, 188 patients were randomly assigned to satralizumab (n=96) or placebo (n=92). 166 AChR-IgG-positive patients (80 in the placebo group and 86 in the satralizumab group) were included in the modified intention-to-treat population. At week 24, statistically significant yet small improvements in MG-ADL score were observed with satralizumab versus placebo (adjusted mean −3·59, 95% CI −4·15 to −3·02 <em>vs</em> −2·57, −3·25 to −1·88; difference −1·02, −1·88 to −0·16; p=0·0120). The proportion of","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Should the preclinical stage of Alzheimer's disease be disclosed?","authors":"Colin L Masters","doi":"10.1016/s1474-4422(24)00520-9","DOIUrl":"https://doi.org/10.1016/s1474-4422(24)00520-9","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"74 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oriane Blanquie, Lorenzo Guizzaro, Ralf Herold, Marion Haberkamp, André Elferink, Pavel Balabanov, Falk Ehmann
{"title":"EU regulatory horizons for Alzheimer's disease","authors":"Oriane Blanquie, Lorenzo Guizzaro, Ralf Herold, Marion Haberkamp, André Elferink, Pavel Balabanov, Falk Ehmann","doi":"10.1016/s1474-4422(25)00004-3","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00004-3","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Elevating the wellbeing of neurologists","authors":"Neil A Busis, Jennifer Bickel, Carlayne E Jackson","doi":"10.1016/s1474-4422(25)00002-x","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00002-x","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Josephine H Pedder, Adam M Sonabend, Michael D Cearns, Benedict D Michael, Rasheed Zakaria, Amy B Heimberger, Michael D Jenkinson, David Dickens
{"title":"Crossing the blood–brain barrier: emerging therapeutic strategies for neurological disease","authors":"Josephine H Pedder, Adam M Sonabend, Michael D Cearns, Benedict D Michael, Rasheed Zakaria, Amy B Heimberger, Michael D Jenkinson, David Dickens","doi":"10.1016/s1474-4422(24)00476-9","DOIUrl":"https://doi.org/10.1016/s1474-4422(24)00476-9","url":null,"abstract":"The blood–brain barrier is a physiological barrier that can prevent both small and complex drugs from reaching the brain to exert a pharmacological effect. For treatment of neurological diseases, drug concentrations at the target site are a fundamental parameter for therapeutic effect; thus, the blood–brain barrier is a major obstacle to overcome. Novel strategies have been developed to circumvent the blood–brain barrier, including CSF delivery, intracranial delivery, ultrasound-based methods, membrane transporters, receptor-mediated transcytosis, and nanotherapeutics. These approaches each have their advantages and disadvantages. CSF delivery and intracranial delivery are direct but invasive techniques that have not yet shown efficacy in clinical trials, although development of novel delivery devices might improve these approaches. Ultrasound-based disruption has shown some efficacy in clinical trials, but it can require invasive procedures. Approaches using membrane transporters and receptor-mediated transcytosis are less invasive than are other techniques, but they can have off-target effects. Nanotherapeutics have shown promise, but these strategies are in early stages of development. Advancements in drug delivery across the blood–brain barrier will require appropriately designed and powered clinical studies, with a focus on the timing of treatment, demographic and genetic considerations, head-to-head comparison with other treatment strategies (rather than a placebo), and relevant primary and secondary outcome measures.","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"74 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
